Mechanisms regulating macrophage functions in both inflammatory and immune responses are under investigation. With regard to nonspecific functions, research has concentrated upon regulation of mediator production by macrophages treated with inflammatory microbial products and soluble mediators. One class of mediators, the colony stimulating factors (CSF), were found to stimulate macrophages to produce both lymphocyte activating factor (interleukin 1) and interferon. Additionally, CSF was found to sensitize macrophages to bacterial lipopolysaccharide through an intermediary interferon priming stage and to modulate a primary immune response in vitro. Preliminary experiments performed with fibroblast supernatants rich in CSF suggest that soluble fibroblast products can also stimulate macrophages to produce a fibroblast activating factor and toxic oxygen metabolites. With regard to specific functions, supernatants from mitogen-stimulated spleen cells were found to enhance macrophage-T lymphocyte cooperation. Active supernatants cnverted phenotypically Ia-antigen negative macrophages to Ia positive cells capable of presenting antigen to T-lymphocytes. Work in progress is designed to further investigate the macrophage regulating activities of CSF, interferon, and the active splenic supernatants.